DE2923553C2 - - Google Patents
Info
- Publication number
- DE2923553C2 DE2923553C2 DE2923553A DE2923553A DE2923553C2 DE 2923553 C2 DE2923553 C2 DE 2923553C2 DE 2923553 A DE2923553 A DE 2923553A DE 2923553 A DE2923553 A DE 2923553A DE 2923553 C2 DE2923553 C2 DE 2923553C2
- Authority
- DE
- Germany
- Prior art keywords
- radical
- substituted
- yield
- pyrrolin
- aryl radical
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- -1 alkyl radical Chemical class 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 15
- 150000001875 compounds Chemical class 0.000 claims description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 125000003107 substituted aryl group Chemical group 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 150000005840 aryl radicals Chemical class 0.000 claims description 8
- 150000002431 hydrogen Chemical class 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- CDCHBOQVXIGZHA-UHFFFAOYSA-N 1,2-dihydropyrrol-5-one Chemical class O=C1NCC=C1 CDCHBOQVXIGZHA-UHFFFAOYSA-N 0.000 claims description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 238000007363 ring formation reaction Methods 0.000 claims 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 239000012429 reaction media Substances 0.000 claims 1
- 125000000547 substituted alkyl group Chemical group 0.000 claims 1
- 238000002844 melting Methods 0.000 description 10
- 230000008018 melting Effects 0.000 description 10
- 239000000126 substance Substances 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 3
- 238000006798 ring closing metathesis reaction Methods 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 238000004140 cleaning Methods 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 2
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 230000020477 pH reduction Effects 0.000 description 2
- HNJBEVLQSNELDL-YZRHJBSPSA-N pyrrolidin-2-one Chemical class O=C1CC[14CH2]N1 HNJBEVLQSNELDL-YZRHJBSPSA-N 0.000 description 2
- 150000003235 pyrrolidines Chemical class 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000010409 thin film Substances 0.000 description 2
- RHNBWZZWDAOBQY-UHFFFAOYSA-N 1,2,4-trimethyl-3-phenyl-2h-pyrrol-5-one Chemical compound CC1N(C)C(=O)C(C)=C1C1=CC=CC=C1 RHNBWZZWDAOBQY-UHFFFAOYSA-N 0.000 description 1
- JWUYOFJPYSNYFC-UHFFFAOYSA-N 1,2-dimethyl-3,4-diphenyl-2h-pyrrol-5-one Chemical compound CC1N(C)C(=O)C(C=2C=CC=CC=2)=C1C1=CC=CC=C1 JWUYOFJPYSNYFC-UHFFFAOYSA-N 0.000 description 1
- QLCPYHKRCGVOOA-UHFFFAOYSA-N 1,2-dimethyl-3-phenyl-2h-pyrrol-5-one Chemical compound CC1N(C)C(=O)C=C1C1=CC=CC=C1 QLCPYHKRCGVOOA-UHFFFAOYSA-N 0.000 description 1
- HHAISVSEJFEWBZ-UHFFFAOYSA-N 1-[4-(trifluoromethyl)phenyl]ethanone Chemical compound CC(=O)C1=CC=C(C(F)(F)F)C=C1 HHAISVSEJFEWBZ-UHFFFAOYSA-N 0.000 description 1
- XMMJINSTYOLCCA-UHFFFAOYSA-N 1-benzyl-3-[4-(trifluoromethyl)phenyl]-2h-pyrrol-5-one Chemical compound C1=CC(C(F)(F)F)=CC=C1C(C1)=CC(=O)N1CC1=CC=CC=C1 XMMJINSTYOLCCA-UHFFFAOYSA-N 0.000 description 1
- IRVWTVRIFOKBIL-UHFFFAOYSA-N 1-benzyl-4-methyl-3-[4-(trifluoromethyl)phenyl]-2h-pyrrol-5-one Chemical compound O=C1C(C)=C(C=2C=CC(=CC=2)C(F)(F)F)CN1CC1=CC=CC=C1 IRVWTVRIFOKBIL-UHFFFAOYSA-N 0.000 description 1
- DHMVUKFVGBQDDA-UHFFFAOYSA-N 1-methyl-3-(4-methylphenyl)-4-phenyl-2h-pyrrol-5-one Chemical compound O=C1N(C)CC(C=2C=CC(C)=CC=2)=C1C1=CC=CC=C1 DHMVUKFVGBQDDA-UHFFFAOYSA-N 0.000 description 1
- SWLVHCWYTKNOAB-UHFFFAOYSA-N 2-(5-oxo-3-phenyl-1,2-dihydropyrrol-4-yl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1C1=C(C=2C=CC=CC=2)CNC1=O SWLVHCWYTKNOAB-UHFFFAOYSA-N 0.000 description 1
- PMGYCIGYLNWVCH-UHFFFAOYSA-N 3-(3,4-dimethoxyphenyl)-4-phenyl-1,2-dihydropyrrol-5-one Chemical compound C1=C(OC)C(OC)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)NC1 PMGYCIGYLNWVCH-UHFFFAOYSA-N 0.000 description 1
- KEMCZWYPWCUGPE-UHFFFAOYSA-N 3-(4-chlorophenyl)-4-phenyl-1,2-dihydropyrrol-5-one Chemical compound C1=CC(Cl)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)NC1 KEMCZWYPWCUGPE-UHFFFAOYSA-N 0.000 description 1
- XIAMSSUQNNNXMH-UHFFFAOYSA-N 3-(4-fluorophenyl)-4-phenyl-1,2-dihydropyrrol-5-one Chemical compound C1=CC(F)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)NC1 XIAMSSUQNNNXMH-UHFFFAOYSA-N 0.000 description 1
- LXZAVFHIIYGLTF-UHFFFAOYSA-N 3-(4-methoxyphenyl)-4-phenyl-1,2-dihydropyrrol-5-one Chemical compound C1=CC(OC)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)NC1 LXZAVFHIIYGLTF-UHFFFAOYSA-N 0.000 description 1
- XRCJTMJEQCHAOB-UHFFFAOYSA-N 3-(4-methylphenyl)-4-phenyl-1,2-dihydropyrrol-5-one Chemical compound C1=CC(C)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)NC1 XRCJTMJEQCHAOB-UHFFFAOYSA-N 0.000 description 1
- JPMRXLUPEVYCNZ-UHFFFAOYSA-N 4-(2-fluorophenyl)-3-[4-(trifluoromethyl)phenyl]-1,2-dihydropyrrol-5-one Chemical compound FC1=CC=CC=C1C1=C(C=2C=CC(=CC=2)C(F)(F)F)CNC1=O JPMRXLUPEVYCNZ-UHFFFAOYSA-N 0.000 description 1
- QZSANDZKAKLRPX-UHFFFAOYSA-N 4-(4-fluorophenyl)-3-[4-(trifluoromethyl)phenyl]-1,2-dihydropyrrol-5-one Chemical compound C1=CC(F)=CC=C1C1=C(C=2C=CC(=CC=2)C(F)(F)F)CNC1=O QZSANDZKAKLRPX-UHFFFAOYSA-N 0.000 description 1
- LIOVPXGQAPGNNY-UHFFFAOYSA-N 4-(4-fluorophenyl)-3-phenyl-1,2-dihydropyrrol-5-one Chemical compound C1=CC(F)=CC=C1C1=C(C=2C=CC=CC=2)CNC1=O LIOVPXGQAPGNNY-UHFFFAOYSA-N 0.000 description 1
- BEOBZEOPTQQELP-UHFFFAOYSA-N 4-(trifluoromethyl)benzaldehyde Chemical compound FC(F)(F)C1=CC=C(C=O)C=C1 BEOBZEOPTQQELP-UHFFFAOYSA-N 0.000 description 1
- DQOSOTIKDZAXKT-UHFFFAOYSA-N 4-phenyl-3-[4-(trifluoromethyl)phenyl]-1,2-dihydropyrrol-5-one Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)NC1 DQOSOTIKDZAXKT-UHFFFAOYSA-N 0.000 description 1
- HOJZEMQCQRPLQQ-UHFFFAOYSA-N 4-phenylpyrrolidin-2-one Chemical compound C1NC(=O)CC1C1=CC=CC=C1 HOJZEMQCQRPLQQ-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- DJEBTLRMBZNIIF-UHFFFAOYSA-N n-phenacyl-2-phenylacetamide Chemical compound C=1C=CC=CC=1C(=O)CNC(=O)CC1=CC=CC=C1 DJEBTLRMBZNIIF-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- DAFOCGYVTAOKAJ-UHFFFAOYSA-N phenibut Chemical compound OC(=O)CC(CN)C1=CC=CC=C1 DAFOCGYVTAOKAJ-UHFFFAOYSA-N 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000002997 prostaglandinlike Effects 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 150000004040 pyrrolidinones Chemical class 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 150000003283 rhodium Chemical class 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/263—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms
- C07D207/267—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/263—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms
- C07D207/27—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/36—Oxygen or sulfur atoms
- C07D207/38—2-Pyrrolones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/54—Quaternary phosphonium compounds
- C07F9/5407—Acyclic saturated phosphonium compounds
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Pyrrole Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Die Erfindung betrifft den Gegenstand des Patenanspruchs.The invention relates to the subject matter of the patent claim.
Die Erfindung schlägt Verfahren zur Herstellung von Verbindungen der allgemeinen Formel (V) vor,The invention proposes methods of making connections the general formula (V),
welche erfindungsgemäß durch Ringschluß von N-substituierten Acetamiden (IV) der allgemeinen Formelwhich according to the invention by ring closure of N-substituted Acetamides (IV) of the general formula
zur Bildung der entsprechenden Verbindung (V) ausgeführt werden. Dieser Ringschluß wird erfindungsgemäß unter Stickstoff in basischer Umgebung ausgeführt, beispielsweise in t-Butanol mit Kalium-t-butoxid als Base mit nachfolgendem Ansäuern mit einer Mineralsäure, wie etwa HCl und Verdünnen mit Wasser.to form the corresponding compound (V) will. This ring closure is according to the invention carried out under nitrogen in a basic environment, for example in t-butanol with potassium t-butoxide as Base with subsequent acidification with a mineral acid, such as HCl and dilution with water.
Es werden die folgenden Definitionen verwendet:
Aryl = Phenyl, Pyridyl, Furyl, Thienyl, N-Alkyl-
oder N-Aryl-pyrrolyl, und die entsprechenden
Benzo-Derivate, d. h. Naphthyl oder Chinolyl;
Alkyl = C₁- bis C₁₆-Kohlenwasserstoffe;
Substituenten (bis zu 5 gleichen oder gemischten) =
Alkyl, Halogenalkyl (z. B. F₃C), O-Alkyl, N-Dialkyl
(gleich oder verschieden), S-Alkyl, Halogen. O-Benzyl,
N-Dibenzyl, N-Alkyl/Benzyl, S-Benzyl, O-Aryl, S-Aryl,
N-Diaryl, N-Alkyl/Benzyl/Aryl, OH, NH₂, SH (wobei
die letzten drei während des basischen Ringschlusses
geschützt sind).The following definitions are used:
Aryl = phenyl, pyridyl, furyl, thienyl, N-alkyl- or N-aryl-pyrrolyl, and the corresponding benzo derivatives, ie naphthyl or quinolyl;
Alkyl = C₁ to C₁₆ hydrocarbons;
Substituents (up to 5 identical or mixed)
Alkyl, haloalkyl (e.g. F₃C), O-alkyl, N-dialkyl (same or different), S-alkyl, halogen. O-benzyl, N-dibenzyl, N-alkyl / benzyl, S-benzyl, O-aryl, S-aryl, N-diaryl, N-alkyl / benzyl / aryl, OH, NH₂, SH (the last three during the basic ring closure are protected).
Einige 3-Pyrrolin-2-on-Abkömmlinge werden gemäß der US-Patent schrift 32 72 842 in folgender Weise hergestellt:Some 3-pyrrolin-2-one derivatives are described in the U.S. patent Font 32 72 842 produced in the following way:
Dabei enthalten R⁵ und R⁵′ nicht Wasserstoff und R⁴ ist stets S-CH₂-(S = Substituent). R⁵ and R⁵ 'do not contain hydrogen and R⁴ is always S-CH₂- (S = substituent).
Wie die folgenden Vergleichsversuche zeigen, ist die Vorgehensweise gemäß dieses US-Patentes jedoch für das der Erfindung zugrundeliegende Substitutions muster ungeeignet (wahrscheinlich ist die sterische Hinderung bei R⁴ = Aryl zu groß; zudem erfolgt Substitution des Wasserstoffes bei R⁵ bzw. R⁵′ und die entstehenden oxidativen Verunreinigungen sind nicht abtrennbar):As the following comparative experiments show, the Procedure according to this US patent, however for the substitution on which the invention is based pattern is unsuitable (probably steric hindrance when R⁴ = aryl too large; moreover the hydrogen is substituted at R⁵ or R⁵ 'and the resulting oxidative impurities cannot be separated):
Es wurde versucht, die erfindungsgemäße ReaktionAn attempt was made to implement the reaction according to the invention
unter gleichen oder analogen Bedingungen wie in den Beispielen 1 und 2 der US-PS 32 72 842 durchzuführen.under the same or analogous conditions as in the Examples 1 and 2 of US-PS 32 72 842 perform.
Dabei ergaben sich die folgenden Beobachtungen, in deren Beschreibung IVa und Va die obigen Verbindungen bedeuten:The following observations resulted, in their description IVa and Va the above compounds mean:
IVa und KOH wurden Xylol während drei Stunden am Rückfluß erhitzt. Die Abwesenheit von IVa, also dessen vollständige Umsetzung, wurde durch Dünnschicht- Chromatographie nachgewiesen. Nachfolgend wurde auf gearbeitet und durch Chromatographie eine teilweise Trennung des Gemisches erzielt. Aus den Fraktionen konnte an in Frage kommenden Verbindungen nur eine Substanz isoliert werden, die aber einen Schmelzpunkt von 256 bis 260°C aufweist. Da die Verbindung Va jedoch einen Schmelzpunkt von 177 bis 179°C aufweist, ist die erzeugte Substanz mit der gesuchten nicht identisch. Die Verbindung Va konnte auch nicht in geringsten Mengen isoliert werden.IVa and KOH were xylene for three hours on Heated to reflux. The absence of IVa complete implementation, was through thin-film Chromatography demonstrated. Below was on worked and by chromatography a partial Separation of the mixture achieved. From the fractions could only have one on the connections in question Substance can be isolated, but a melting point from 256 to 260 ° C. Since the connection Va however has a melting point of 177 to 179 ° C, is not the substance produced with the sought identical. The connection Va could not in the least Amounts are isolated.
IVa wurde mit zwei Äquivalenten NaH in Toluol unter Rückfluß am Wasserabscheider erhitzt. Die Toluolphase wurde aufgearbeitet und ergab eine Ausbeute von 32% neutralen Produkten sowie nach Ansäuern und Extraktion der Wasserphase noch einmal 32% an sauren Produkten. Die ausschließlich in Frage kommenden neutralen Produkte wurden an Silicagel chromatographiert. Aus den möglicherweise relevanten Fraktionen 3 und 4 konnte nur eine Verbindung mit Schmelzpunkt 273°C und einem wahrscheinlichen Molekulargewicht (MG) von 323 (m/e 323, 85, 83) isoliert werden. Da die gesuchte Verbindung Va einen Schmelzpunkt von 177 bis 179°C und ein Molekulargewicht von 235 (m/e 235, 206, 191, 178, 104) aufweist, wurde sie auch in diesem analogen Versuch nicht erzeugt.IVa was submerged in toluene with two equivalents of NaH Reflux heated at the water separator. The toluene phase was worked up and gave a yield of 32% neutral products as well as after acidification and extraction in the water phase again 32% of acidic products. The only neutral ones in question Products were chromatographed on silica gel. From the possibly relevant fractions 3 and 4 could only connect with a melting point of 273 ° C and a probable molecular weight (MW) of 323 (m / e 323, 85, 83) can be isolated. Because the one you are looking for Compound Va has a melting point of 177 to 179 ° C and a molecular weight of 235 (m / e 235, 206, 191, 178, 104), it was also used in this analog Attempt not generated.
Damit ist das Beispiel 1 der entgegengehaltenen US-PS 32 72 842 ungeeignet zur Herstellung der Verbindung Va. This is example 1 of the US patent cited 32 72 842 unsuitable for making the connection Va.
IVa wurde zu 2,2 Äquivalenten EtONa in EtOH gegeben. Entgegen der Lehre der US-PS wurde keine Reaktion bei Raumtemperatur beobachtet. Nachfolgend wurde während 30 Minuten auf Rückfluß erhitzt; danach war IVa mittels DC nicht mehr nachweisbar. Die rote Lösung wurde in zwei Teile A und B geteilt. Teil B wurde mit Wasser auf 1 : 1 verdünnt und mit Chloroform extrahiert (75% Ausbeute). Umkristallisation des Extraktes aus Benzol ergab eine 32%ige Ausbeute von verunreinigtem Va (nach DC). Nach Chromatographie der Mutterlaugen konnten weitere 10% Va gewonnen werden. Teil A wurde angesäuert und mit Wasser weiter auf 1 : 1 verdünnt, dies ergab 46% Rohausbeute, weitere Verdünnung ergab nochmals 27% Rohausbeute (Total 73% Rohausbeute) von verunreinigtem Va. Beide Produkte waren jedoch für die unveränderte Weiterverarbeitung zu unrein. Eine Abtrennung der begleitenden Oxidations-Nebenprodukte erwies sich als praktisch nicht durchführbar (Konrolle mit DC).IVa was added to 2.2 equivalents of EtONa in EtOH. Contrary to the teaching of the US PS, there was no response Room temperature observed. Subsequently, during Heated to reflux for 30 minutes; after that IVa was mean DC no longer detectable. The red solution was divided into two parts A and B. Part B was made with water diluted to 1: 1 and extracted with chloroform (75% yield). Recrystallization of the extract Benzene gave a 32% yield of contaminated Va (after DC). After chromatography of the mother liquors a further 10% Va could be gained. Part A was acidified and further diluted with water to 1: 1, this gave 46% crude yield, further dilution gave another 27% raw yield (total 73% raw yield) of contaminated Va. However, both products were too impure for unchanged processing. A separation of the accompanying oxidation by-products turned out to be practically impractical (Control with DC).
Eine Durchführung nach dieser Vorschrift führte nur dann zu Produkten von ausreichender Reinheit für die direkte Weiterverarbeitung, wenn zusätzlich unter Sauerstoffausschluß, d. h. unter Stickstoff gearbeitet wurde.An implementation according to this regulation only led then to products of sufficient purity for the direct processing, if additional under Exclusion of oxygen, d. H. worked under nitrogen has been.
IVa wurde zu 3,3 Äquivalenten t-BuOK in t-BuOH gegeben und eine Stunde auf Rückfluß gehalten. Nach Abkühlung wurde ein rotes Kaliumsalz isoliert, das in Wasser suspendiert und angesäuert wurde. Das isolierte Rohprodukt wurde an Silicagel chromatographiert. Aus einer ersten Fraktion konnte eine Verbindung mit Schmelzpunkt 158 bis 160°C und MG 250 (m/e 250, 222, 178) rein isoliert werden. Aus einer zweiten Fraktion konnte eine gelbe Substanz mit Schmelzpunkt 330°C und MG 466 (m/e 466, 281, 267, 243, 207) gewonnen werden. Wiederholte Chromatographie ergab eine zweite gelbe, noch polarere Substanz mit Schmelzpunkt 320°C und MG 466 (m/e 466, 281, 207, 149, 135). Eine Substanz mit dem Schmelzpunkt und dem Molekulargewicht der Verbindung Va konnte nicht isoliert werden.IVa was added to 3.3 equivalents of t-BuOK in t-BuOH and held at reflux for an hour. After cooling a red potassium salt was isolated, which in Water was suspended and acidified. The isolated Crude product was chromatographed on silica gel. A first faction was able to connect with Melting point 158 to 160 ° C and MG 250 (m / e 250, 222, 178) can be isolated. From a second fraction could a yellow substance with melting point 330 ° C and MG 466 (m / e 466, 281, 267, 243, 207) will. Repeated chromatography gave a second yellow, more polar substance with melting point 320 ° C and MG 466 (m / e 466, 281, 207, 149, 135). A substance with the melting point and molecular weight the compound Va could not be isolated.
Damit erweist sich auch das Beispiel 2 der US-PS 32 72 842 als ungeeignet für die nach dem erfindungsgemäßen Verfahren erhältlichen Substanzen.This also proves Example 2 of the US PS 32 72 842 as unsuitable for that according to the invention Process available substances.
Aus Chemical Abstracts 75 (1971), 98437 u. ist ein Verfahren der im Oberbegriff des Hauptanspruches genannten Art bekannt.From Chemical Abstracts 75 (1971), 98437 u. is a Procedure in the preamble of the main claim known type known.
Aus dem Referat geht hervor, daß 4-Phenyl-2-pyrrolidinon in 94,3%iger Ausbeute aus γ-Amino-β-phenylbuttersäure erhältlich sei. Dieses Ausgangsmaterial, GABA genannt, wird jedoch in der Praxis aus dem Pyrrolidon hergestellt, nicht etwa umgekehrt. Der Grund dafür liegt darin, daß die neutralen Pyrrolidone direkt gebildet werden, und einfacher zu reinigen sind, und daß die nachfolgende Hydrolyse zur Aminosäure normalerweise ohne Nebenprodukte ab läuft. The paper shows that 4-phenyl-2-pyrrolidinone can be obtained in 94.3% yield from γ- amino- β- phenylbutyric acid. In practice, this starting material, called GABA, is produced from pyrrolidone, not the other way around. The reason for this is that the neutral pyrrolidones are formed directly and are easier to clean, and that the subsequent hydrolysis to the amino acid normally takes place without by-products.
Demgemäß wird GABA nach bisherigen Verfahren von praktischer Bedeutung gemäß dem folgenden Schema A oder Schema B erhalten, wobei als Ausgangsmaterial jeweils der entsprechende Aldehyd verwendet wird. Dabei sind die Ausbeuten der verschiedenen Reaktions stufen teilweise sehr gering und die Reinigung der Zwischen- und Endstufen oft aufwendig, so bei Destillation von nicht-kristallinen Verbindungen. Accordingly, GABA is used according to the previous methods of practical importance according to the following scheme A or Scheme B obtained, starting material the corresponding aldehyde is used in each case. Here are the yields of the various reactions partially very low and the cleaning the intermediate and final stages are often complex, so at Distillation of non-crystalline compounds.
Das erfindungsgemäße Verfahren geht demgegenüber aus von den stabileren und meistens leichter zugänglichen Ketonen. So ist z. B. 4-Trifluormethylacetophenon im Handel erhältlich, nicht jedoch 4-Tri-fluormethyl-benzaldehyd. Die Ausbeuten sind durchweg hoch und die Zwischenprodukte fallen ohne Reinigung in genügender Reinheit an. Die Synthese folgt zunächst dem bekannten Syntheseweg von Chlor amphenicol. Die Literatur beschreibt jedoch für die beiden letzten Stufen keine Verfahren, die kommerziell auswertbar wären. Im Falle von R³≠H erhält man erfindungsgemäß ausschließlich Verbindungen mit 3,4-cis-Substitution, wogegen die früheren Verfahren vorwiegend die thermodynamisch stabilere trans-Verbindung ergeben.The method according to the invention is in contrast out of the more stable and mostly more accessible Ketones. So z. B. 4-trifluoromethyl acetophenone commercially available, but not 4-tri-fluoromethyl benzaldehyde. The yields are consistently high and the intermediates fall without Cleaning in sufficient purity. The synthesis initially follows the well-known synthetic route of chlorine amphenicol. However, the literature describes for the The last two stages have no commercial procedures would be evaluable. In the case of R³ ≠ H receives only compounds with 3,4-cis substitution, whereas the previous methods predominantly the thermodynamically more stable trans connection result.
Ein Bedürfnis nach einem in der Praxis einsetzbaren Verfahren ergibt sich aus dem Vorstehenden. Ausschlaggebend dafür ist nicht allein die Anzahl der notwendigen Verfahrenschritte. Vielmehr sind ebenso die Zugänglichkeit der Ausgangsverbindungen, der Aufwand für die einzelnen Schritte, Reinheit des Endprodukts u. a. zu berücksichtigen. Reinstes Pyrrolidon war z. B. nach Schema B nach Dünnschicht chromatographie nicht zu erhalten, wohl weil die Raney-Nickel-Hydrierung nicht vollständig aushydrierte oder wegen anderweitiger prinzipieller Unzulänglichkeiten dieses Verfahrens.A need for one that can be used in practice The procedure follows from the above. Decisive this is not just the number of necessary procedural steps. Rather are the same the accessibility of the output connections, the Effort for the individual steps, purity of the End product u. a. to consider. Purest pyrrolidone was z. B. according to scheme B according to thin film not get chromatography, probably because of that Raney nickel hydrogenation did not fully hydrogenate or because of other fundamental shortcomings this procedure.
Demgegenüber verläuft das erfindungsgemäße Verfahren mit folgenden Vorteilen: In contrast, the method according to the invention proceeds with the following advantages:
- 1. Leichter zugängliche Ausgangsverbindungen.1. Easier accessible source connections.
- 2. Kristalline Zwischenprodukte und damit keine Destillation mit deren Nachteilen und Aufwand.2. Crystalline intermediates and therefore none Distillation with its disadvantages and effort.
- 3. Reinste Endprodukte.3. Purest end products.
- 4. Im Falle von R³ = Aryl oder substituiertes Aryl erhält man ausschließlich 3,4-cis-Verbindungen mit weit besserer Ausbeute.4. In the case of R³ = aryl or substituted aryl only 3,4-cis compounds are obtained with far better yield.
- 5. Eine Druckhydrierung mit deren Nachteilen wird vermieden.5. Pressure hydration with its disadvantages avoided.
Zu den Pyrrolidin-2-on-Abkömmlingen der allgemeinen FormelTo the pyrrolidin-2-one derivatives of the general formula
und ihren entsprechenden Pyrrolidinen (II) der allgemeinen Formeland their corresponding pyrrolidines (II) of the general formula
wobei
R¹ = Wasserstoff, einen Alkylrest, substituierten Alkylrest,
Arylrest oder substituierten Arylrest
R³ = Wasserstoff, Alkylrest, substituierten Alkylrest,
Arylrest oder substituierten Arylrest;
R⁴ = Arylrest oder substituierten Arylrest;
R⁵ = Wasserstoff, Alkylrest, substituierten Alkylrest,
Arylrest oder substituierten Arylrest;
R⁵′ = Wasserstoff, Alkylrest oder substituierten
Alkylrest bedeuten und die an den erfindungsgemäß
herstellbaren Zwischenprodukten erhalten werden können, gehören
viele bekannte Verbindungen, die interessante ZNS-Aktivität
entwickeln (Archivum Immunologiae et Therapiae
Experimentalis 1975, 23, 733-751. Viele
der Verbindungen (I) zeigen eine prostaglandin
ähnliche Aktivität (DE-OS 25 27 989).in which
R¹ = hydrogen, an alkyl radical, substituted alkyl radical, aryl radical or substituted aryl radical R³ = hydrogen, alkyl radical, substituted alkyl radical, aryl radical or substituted aryl radical; R⁴ = aryl radical or substituted aryl radical; R⁵ = hydrogen, alkyl radical, substituted alkyl radical, aryl radical or substituted aryl radical; R⁵ ′ = hydrogen, alkyl radical or substituted alkyl radical and which can be obtained from the intermediates which can be prepared according to the invention include many known compounds which develop interesting CNS activity (Archivum Immunologiae et Therapiae Experimentalis 1975, 23, 733-751. Many of the compounds ( I) show a prostaglandin-like activity (DE-OS 25 27 989).
Gemäß der DE-OS 29 54 236 sind allgemein gesprochen die 3-4-cis-substituierten, nach Wahl optisch aktiven Pyrrolidin-2-on-Abkömmlinge der Formel I, nämlichAccording to DE-OS 29 54 236 are spoken generally the 3-4-cis-substituted, optically active at choice Pyrrolidin-2-one derivatives of formula I, namely
oder nach Isomerisierungor after isomerization
durch Hydrierung von 3-Pyrrolin-2-on-Abkömmlingen der eingangs schon genannten Formel (V)by hydrogenation of 3-pyrrolin-2-one derivatives of Formula (V) already mentioned at the beginning
erhältlich, worin R¹, R³, R⁴, R⁵ sowie R⁵′ in gleicher Weise wie oben stehend definiert sind, wobei nach Wahl auch ein geeigneter optisch aktiver Katalysator (Angew. Chem. 83, 956 (1971)) oder ein eingebautes asymmetrisches Zentrum von C-5 von (V) verwendet werden können. available in which R¹, R³, R⁴, R⁵ and R⁵ ′ are defined in the same way as above, with a suitable optically active one Catalyst (Angew. Chem. 83, 956 (1971)) or a built-in asymmetric center of C-5 of (V) can be used.
Das auf die oben erläuterte Weise hergestellte 3-Pyrrolin-2-on-Derivat (V) kann leicht mit beispielsweise PD/C, Pt oder chiralen Rhodiumkomplexen als Katalysator in Alkohol (vorzugsweise Methanol-Lösung) zu dem ZNS-aktiven substituierten Pyrrolidin- 2-on-Abkömmling (I-cis) hydriert werden. Diese Reaktionsfolge hat den Vorteil, daß Derivate erhalten werden, bei denen R³ und R⁴ ausschließlich als cis-Substituenten gewonnen werden. Die (I-cis)-Verbindungen können in die entsprechenden (I-trans)-Verbindungen durch Basen- oder Säurebehandlung umgesetzt werden. The one manufactured in the manner explained above 3-pyrrolin-2-one derivative (V) can easily be used for example PD / C, Pt or chiral rhodium complexes as a catalyst in alcohol (preferably methanol solution) to the CNS-active substituted pyrrolidine 2-one derivative (I-cis) are hydrogenated. This sequence of reactions has the advantage that derivatives are obtained are, in which R³ and R⁴ exclusively as cis substituents can be obtained. The (I-cis) compounds can in the corresponding (I-trans) compounds implemented by base or acid treatment will.
Die nachfolgenden Beispiele erläutern das erfindungsgemäße Verfahren.The following examples explain the invention Method.
Eine Lösung von 12,6 g (50 m Mol) von 2-Phenyl acetamidoacetophenon in 200 ml t-Butanol wird einer Rückflußlösung von Kalium-t-butoxid zugegeben, welche aus 6,5 g Kalium (166 m Mol) und 200 ml t-Butanol unter Stickstoff hergestellt wurde. Nach 40 Minuten Rückfluß wird die Lösung auf 40°C abgekühlt und mit 2n HCl (etwa 120 ml) mindestens auf pH 6 bis 5 ange säuert. Die gebildete Suspension wird in 3 Liter Eiswasser geschüttet. Der Niederschlag wird aufgesammelt und mit Wasser gewaschen. Nach dem Trocknen werden 9,85 g (84,1%) von (Va) mit einem Schmelzpunkt (SP) von 183-90°C erhalten. Die Extraktion des Wassers mit Chloroform ergibt zusätzlich 1,3 g (11,1%) von (Va). Eine rekristallisierte Probe aus Benzol zeigte einen Schmelzpunkt von 177-9°C.A solution of 12.6 g (50 moles) of 2-phenyl acetamidoacetophenone in 200 ml of t-butanol becomes one Reflux solution of potassium t-butoxide added, which from 6.5 g of potassium (166 m mol) and 200 ml of t-butanol was made under nitrogen. After 40 minutes The solution is refluxed to 40 ° C. and cooled 2N HCl (about 120 ml) at least to pH 6 to 5 acidifies. The suspension formed is in 3 liters of ice water poured. The precipitation is collected and washed with water. After drying 9.85 g (84.1%) of (Va) with a melting point (SP) obtained from 183-90 ° C. The extraction of the water with Chloroform also gives 1.3 g (11.1%) of (Va). A recrystallized sample from benzene showed one Melting point of 177-9 ° C.
Die folgenden Verbindungen der Formel (V) wurden analog hergestellt.The following compounds of formula (V) were analogous produced.
3-Phenyl-4-(4′-chlorphenyl)-3-pyrrolin-2-on (Vb),
SP 204-10°C, Ausbeute 100%,
3-(2′-Carboxyphenyl)-4-phenyl-3-pyrrolin-2-on (Vc),
SP 238-41°C, Ausbeute 89%,
3-Phenyl-4-(4′-fluorphenyl)-3-pyrrolin-2-on (Vd),
SP 200-2°C, Ausbeute 95%,
3-(4′-Fluorphenyl)-4-phenyl-3-pyrrolin-2-on (Ve),
SP 199-209°C, Ausbeute 83%,
3-Phenyl-4-(4′-methylphenyl)-3-pyrrolin-2-on (Vf),
SP 210-20°C, Ausbeute 93%,
3-Phenyl-4-(4′-trifluormethylphenyl)-3-pyrrolin-2-on (Vg),
SP 195-8°C, Ausbeute 100%,
3-(2′-Fluorphenyl)-4-(4′-trifluormethylphenyl)-3-
pyrrolin-2-on (Vh),
SP 165-6°C, Ausbeute 98%,
1,3,5-Trimethyl-4-phenyl-3-pyrrolin-2-on (Vi),
SP 79-81°C, Ausbeute 78% nach Kristallisation,
1-Benzyl-4-(4′-trifluormethylphenyl)-3-pyrrolin-2-on (Vk),
gummiartig, Ausbeute ca. 50% (Reaktion nach 5 Stunden
abgebrochen),
1-Benzyl-3-methyl-4-(4′-trifluormethylphenyl)-3-
pyrrolin-2-on (Vl),
gummiartig, Ausbeute 96%,
1,5-Dimethyl-3,4-diphenyl-3-pyrrolin-2-on (Vm),
SP 95-103°C, Ausbeute 100%,
1,5-Dimethyl-4-phenyl-3-pyrrolin-2-on (Vn),
SP 130-5°C, Ausbeute 55% nach Kristallisation,
1-Methyl-3-phenyl-4-(4′-methylphenyl)-3-pyrrolin-2-on
(Vo), SP 123-4°C, Ausbeute 48% nach Kristallisation,
3-Phenyl-4-(4′-methoxyphenyl)-3-pyrrolin-2-on (Vp),
SP 179-81°C, Ausbeute 97%,
3-Phenyl-4-(3′,4′-dimethoxyphenyl)-3-pyrrolin-2-on (Vq),
SP 202-4°C, Ausbeute 97%,
3-(4′-Fluorphenyl)-4-(4′trifluormethylphenyl)-3-
pyrrolin-2-on (Vu),
SP 212-3°C, Ausbeute 100%.3-phenyl-4- (4'-chlorophenyl) -3-pyrrolin-2-one (Vb), SP 204-10 ° C, yield 100%,
3- (2'-carboxyphenyl) -4-phenyl-3-pyrrolin-2-one (Vc), SP 238-41 ° C, yield 89%,
3-phenyl-4- (4'-fluorophenyl) -3-pyrrolin-2-one (Vd), SP 200-2 ° C, yield 95%,
3- (4′-fluorophenyl) -4-phenyl-3-pyrrolin-2-one (Ve), SP 199-209 ° C, yield 83%,
3-phenyl-4- (4'-methylphenyl) -3-pyrrolin-2-one (Vf), SP 210-20 ° C, yield 93%,
3-phenyl-4- (4'-trifluoromethylphenyl) -3-pyrrolin-2-one (Vg), SP 195-8 ° C, yield 100%,
3- (2'-fluorophenyl) -4- (4'-trifluoromethylphenyl) -3- pyrrolin-2-one (Vh), SP 165-6 ° C, yield 98%,
1,3,5-trimethyl-4-phenyl-3-pyrrolin-2-one (Vi), SP 79-81 ° C, yield 78% after crystallization,
1-benzyl-4- (4′-trifluoromethylphenyl) -3-pyrrolin-2-one (Vk), rubbery, yield approx. 50% (reaction terminated after 5 hours),
1-benzyl-3-methyl-4- (4'-trifluoromethylphenyl) -3-pyrrolin-2-one (VI), rubbery, yield 96%,
1,5-dimethyl-3,4-diphenyl-3-pyrrolin-2-one (Vm), SP 95-103 ° C, yield 100%,
1,5-dimethyl-4-phenyl-3-pyrrolin-2-one (Vn), SP 130-5 ° C, yield 55% after crystallization,
1-methyl-3-phenyl-4- (4'-methylphenyl) -3-pyrrolin-2-one (Vo), SP 123-4 ° C, yield 48% after crystallization,
3-phenyl-4- (4'-methoxyphenyl) -3-pyrrolin-2-one (Vp), SP 179-81 ° C, yield 97%,
3-phenyl-4- (3 ′, 4′-dimethoxyphenyl) -3-pyrrolin-2-one (Vq), SP 202-4 ° C, yield 97%,
3- (4'-fluorophenyl) -4- (4'trifluoromethylphenyl) -3- pyrrolin-2-one (Vu), SP 212-3 ° C, yield 100%.
Claims (3)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US91468278A | 1978-06-12 | 1978-06-12 | |
| US1249679A | 1979-02-15 | 1979-02-15 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE2923553A1 DE2923553A1 (en) | 1979-12-20 |
| DE2923553C2 true DE2923553C2 (en) | 1988-06-01 |
Family
ID=26683628
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19792923553 Granted DE2923553A1 (en) | 1978-06-12 | 1979-06-09 | PROCESS FOR THE PREPARATION OF DELTA HOCH 3 -PYRROLIN- (2) DERIVATIVES AND USE OF DELTA HOCH 3 -PYRROLIN- (2) DERIVATIVES FOR THE PRODUCTION OF PYRROLIDONE- (2) DERIVATIVES |
| DE2954237A Expired DE2954237C2 (en) | 1978-06-12 | 1979-06-09 | |
| DE2954236A Expired DE2954236C2 (en) | 1978-06-12 | 1979-06-09 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE2954237A Expired DE2954237C2 (en) | 1978-06-12 | 1979-06-09 | |
| DE2954236A Expired DE2954236C2 (en) | 1978-06-12 | 1979-06-09 |
Country Status (19)
| Country | Link |
|---|---|
| AR (1) | AR222997A1 (en) |
| AT (1) | ATA386679A (en) |
| AU (1) | AU529479B2 (en) |
| CA (1) | CA1108628A (en) |
| CH (1) | CH650772A5 (en) |
| DE (3) | DE2923553A1 (en) |
| DK (1) | DK157847C (en) |
| ES (1) | ES481315A1 (en) |
| FI (1) | FI70209C (en) |
| FR (1) | FR2434151A1 (en) |
| GB (1) | GB2028307B (en) |
| GR (1) | GR68438B (en) |
| IL (1) | IL57266A (en) |
| IT (1) | IT1116891B (en) |
| NL (1) | NL7904584A (en) |
| NO (1) | NO791943L (en) |
| NZ (1) | NZ190705A (en) |
| PT (1) | PT69716A (en) |
| SE (1) | SE431644B (en) |
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|---|---|---|---|---|
| US4943640A (en) * | 1983-10-14 | 1990-07-24 | The Dow Chemical Company | Preparation of 5-(1-alkyl-carbonyloxy)alkylpyrrolidin-2-one |
| AU4809390A (en) * | 1988-12-27 | 1990-08-01 | Ici Americas Inc. | Process for the preparation of 3-carboalkoxypyrrolidones |
| US5021587A (en) * | 1990-01-24 | 1991-06-04 | Petrolite Corporation | Synthesis of N,3,4-trisubstituted-3-azoline-2-ones |
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|---|---|---|---|---|
| US3272842A (en) * | 1965-06-25 | 1966-09-13 | Lilly Co Eli | Novel pyrrolinones |
| GB1350582A (en) | 1970-07-24 | 1974-04-18 | Ucb Sa | Cerivatives of 2-pyrrolidinone |
| DE2413935A1 (en) * | 1974-03-20 | 1975-10-16 | Schering Ag | 4- (POLYALCOXY-PHENYL) -2-PYRROLIDONE |
-
1979
- 1979-05-14 IL IL57266A patent/IL57266A/en unknown
- 1979-05-15 GR GR59088A patent/GR68438B/el unknown
- 1979-05-17 AR AR276559A patent/AR222997A1/en active
- 1979-05-28 AT AT793866A patent/ATA386679A/en not_active Application Discontinuation
- 1979-06-01 PT PT69716A patent/PT69716A/en unknown
- 1979-06-01 AU AU47670/79A patent/AU529479B2/en not_active Ceased
- 1979-06-06 ES ES481315A patent/ES481315A1/en not_active Expired
- 1979-06-08 CA CA329,322A patent/CA1108628A/en not_active Expired
- 1979-06-09 DE DE19792923553 patent/DE2923553A1/en active Granted
- 1979-06-09 DE DE2954237A patent/DE2954237C2/de not_active Expired
- 1979-06-09 DE DE2954236A patent/DE2954236C2/de not_active Expired
- 1979-06-11 GB GB7920275A patent/GB2028307B/en not_active Expired
- 1979-06-11 FR FR7914907A patent/FR2434151A1/en active Granted
- 1979-06-11 NO NO791943A patent/NO791943L/en unknown
- 1979-06-11 SE SE7905079A patent/SE431644B/en not_active IP Right Cessation
- 1979-06-11 DK DK241779A patent/DK157847C/en not_active IP Right Cessation
- 1979-06-11 IT IT49373/79A patent/IT1116891B/en active
- 1979-06-12 FI FI791866A patent/FI70209C/en not_active IP Right Cessation
- 1979-06-12 NL NL7904584A patent/NL7904584A/en not_active Application Discontinuation
- 1979-06-12 CH CH5496/79A patent/CH650772A5/en not_active IP Right Cessation
- 1979-06-12 NZ NZ190705A patent/NZ190705A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| GB2028307A (en) | 1980-03-05 |
| IT7949373A0 (en) | 1979-06-11 |
| FI70209C (en) | 1986-09-15 |
| ES481315A1 (en) | 1980-08-16 |
| IL57266A (en) | 1982-12-31 |
| GR68438B (en) | 1981-12-30 |
| FI70209B (en) | 1986-02-28 |
| FI791866A (en) | 1979-12-13 |
| DK241779A (en) | 1979-12-13 |
| SE7905079L (en) | 1979-12-13 |
| AU529479B2 (en) | 1983-06-09 |
| SE431644B (en) | 1984-02-20 |
| DE2954237C2 (en) | 1989-09-21 |
| DK157847B (en) | 1990-02-26 |
| DK157847C (en) | 1990-09-17 |
| NZ190705A (en) | 1981-10-19 |
| AU4767079A (en) | 1979-12-20 |
| CH650772A5 (en) | 1985-08-15 |
| FR2434151A1 (en) | 1980-03-21 |
| CA1108628A (en) | 1981-09-08 |
| PT69716A (en) | 1979-07-01 |
| DE2954236C2 (en) | 1988-10-06 |
| ATA386679A (en) | 1983-12-15 |
| DE2923553A1 (en) | 1979-12-20 |
| AR222997A1 (en) | 1981-07-15 |
| NL7904584A (en) | 1979-12-14 |
| NO791943L (en) | 1979-12-13 |
| GB2028307B (en) | 1983-01-19 |
| IT1116891B (en) | 1986-02-10 |
| IL57266A0 (en) | 1979-09-30 |
| FR2434151B3 (en) | 1982-04-30 |
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